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Mifepristone Utilization in Cushing's from Large Bilateral Adrenal

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Mifepristone Utilization in Cushing's from Large Bilateral Adrenal Elmer ress Case Report J Endocrinol Metab. 2015;5(3):226-228 Mifepristone Utilization in Cushing’s From Large Bilateral Adrenal Adenoma Prior to Surgery Vasudev Magajia, d, Sarah Parkb, Katie Mastorisb, Maura Bucciarellib, Scott Bemanc Abstract Cushing’s medical management prior to surgery. Mifepristone; Cushing’s syndrome; Bilateral adrenal ad- Utilization of mifepristone was described to mitigate hypercorti- Keywords: enoma solism from bilateral adrenal Cushing’s syndrome. A 47-year-old female on abdominal pain evaluation with CT was found to have a 5.4 × 1.7 × 4.9 cm right adrenal nodule and a 4.3 × 2.9 × 3.3 cm left adrenal nodule with calcification on CT scan with each having density of -3 Housefield units. She had hypercortisolism with testing Introduction revealing high urine free cortisol, unsuppressed cortisol on 1 mg and 8 mg overnight dexamethasone suppression testing, high 11 pm sali- Cushing’s syndrome characterized by glucocorticoid excess vary cortisol × 2 along with elevated random cortisol and undetect- causes weight gain, hypertension, muscular weakness, glucose able ACTH. Her DHEA-S, plasma metanephrine, and rostenedione, metabolism imbalance, proximal muscle weakness, poor tis- renin and aldosterone levels were normal. Adrenal venous sampling sue healing and increased susceptibility to infection. Cushing’s for lateralization of hypercortisolism source using dexamethasone 2 syndrome not only presents challenges in identifying the cause mg PO Q 6 hours × 1 day, showed adrenal vein epinephrine levels of glucocorticoid excess but also presents unique management step up > 100 pg/mL, indicating successful catheterization. Each side challenges. We present a case detailing diagnostic challenges adrenal vein to vena caval cortisol ratio > 4 was consistent with au- of Cushing’s syndrome resulting from bilateral ACTH-inde- tonomous cortisol secretion and left to right adrenal cortisol ratio < pendent macronodular adrenal hyperplasia, unique and novel 2 suggested bilateral adrenal Cushing’s syndrome. She had multiple management strategy of using mifepristone to mitigate hy- co-morbidities including uncontrolled hypertension, poor functional percortisolism and its effects including weight, hypertension, status requiring walker and cane, chronic non-healing cellulitis, glu- secondary infection for preoperative management of clinical cose intolerance and hypokalemia. Mifepristone was initiated for manifestations of Cushing’s syndrome. This not only helped in medical management of hypercortisolism prior to surgery, resulting preparing the patient for surgery, addressed the increased risk in > 50 lbs weight loss, improved blood pressure, complete healing of factors for the surgery but also potentially expedited postop- chronic lower extremity cellulitis and independent ambulation within erative recovery by avoiding effects of abrupt glucocorticoid 4 months. Initially right adrenal adenoma and then left adrenal ad- withdrawal following surgery. enoma were resected in two separate surgeries and pathology showed bilateral enlarged adrenal glands with multiple adrenocortical nodules without adrenal carcinoma. Mifepristone, FDA approved for inoper- Case Report able Cushing’s, facilitated pre-surgery optimization by effectively mitigating hypercortisolism. Mifepristone was utilized as a bridge for A 47-year-old female with past medical history significant for hypertension, hyperlipidemia, glucose intolerance, carotid ar- Manuscript accepted for publication June 24, 2015 tery disease, peripheral vascular disease, coronary artery by- pass grafting, and chronic leg cellulitis presented with abdomi- aDivision of Endocrinology, Department of Medicine, Lehigh Valley Health nal pain. Her CT scan of abdomen showed right adrenal nodule Network, Allentown, PA 18103, USA 1.8 × 4.9 cm and left adrenal nodule 2.8 × 4.3 cm (Fig. 1). She bDepartment of Medicine, Lehigh Valley Health Network, Allentown, PA had workup for pheochromocytoma and hyperaldosteronism 18103, USA was negative but was positive for Cushing’s syndrome (Table cDepartment of Surgery, Lehigh Valley Health Network, Allentown, PA 1). 18103, USA Surgery team evaluated the patient and recommended dCorresponding Author: Vasudev G. Magaji, Division of Endocrinology, De- partment of Medicine, Lehigh Valley Health Network, Allentown, PA 18103, right adrenalectomy, which was the larger of the two adeno- USA. Email: [email protected] mas. However, to assess if one of the adrenal nodule was pro- ducing excessive cortisol, adrenal venous sampling (AVS) was doi: http://dx.doi.org/10.14740/jem288w performed using dexamethasone 2 mg oral every 6 h for 24 h Articles © The authors | Journal compilation © J Endocrinol Metab and Elmer Press Inc™ | www.jofem.org 226 This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited Magaji et al J Endocrinol Metab. 2015;5(3):226-228 Figure 1. Right adrenal adenoma measuring 17.5 × 48.7 mm and left adrenal adenoma with focus of calcification measuring 43 × 28.3 mm. preceding the procedure (Table 2). Patient stopped taking mifepristone one week prior to the right Difference in adrenal gland epinephrine levels compared adrenalectomy. Perioperatively, she was placed on hydrocor- to peripheral levels was > 100 pg/mL, suggesting successful tisone and eventually tapered off. After her right adrenal sur- localization of the catheter. Adrenal vein to peripheral vein gery, she did not require hydrocortisone. Symptomatically she cortisol ratio > 4 was consistent with cortisol hypersecretion. had increased energy level, nausea and weakness resolution. Ratio of left to right adrenal cortisol levels < 2 was diagnos- Pathology showed a right adrenal cortical adenoma measuring tic of bilateral cortisol hypersecretion [1]. It was determined 6.5 × 5.0 × 1.7 cm larger than on the CT scan dimension con- patient should undergo right adrenalectomy as it was larger in taining multiple adrenocortical nodules without any evidence size compared to the left adrenal adenoma. of mitosis, necrosis or vascular invasion and the immunostain- The procedure was deferred as patient needed carotid ing was negative for adrenal carcinoma. After the first surgery, artery surgery initially but the adrenal surgery was deferred the patient expectedly had persistent hypercortisolism and since the patient had multiple co-morbidities directly resulting mifepristone was reinitiated. Seven months later the patient from hypercortisolism. She had several co-morbidities includ- opted to go for second surgery after consideration of continued ing uncontrolled hypertension on metoprolol and lisinopril, medical management with mifepristone. The surgical pathol- hypokalemia on potassium supplements, chronic leg cellulitis ogy revealed a left adrenal cortical adenoma measuring 4.5 × despite being on multiple antiobiotic courses for 10 months, 2.6 × 2.3 cm. Adrenal insufficiency following her left adrenal glucose intolerance, and poor functional status requiring walk- surgery is being managed by hydrocortisone. er and cane. Ketoconazole was contraindicated for interactions with plavix and atorvastatin which could not discontinue due to her severe vascular disease. Mifepristone was initiated at Discussion 300 mg PO every other day and titrated up to once daily. She had 65 lbs (240 lbs to 175 lb) weight loss, hypertension im- This case had unique diagnostic dilemmas, initially the pa- proved, had complete healing of cellulitis, and could ambulate tient’s source of hypercortisolism needed to be determined. independently by 4 months of starting mifepristone. Her po- The right adrenal adenoma was larger than the left adrenal tassium, liver function tests and BP were monitored closely. tumor but the cortisol levels in the left were higher during Table 1. Adrenal Adenoma Functional Evaluation Test (normal range) Result 24-h urine free cortisol (4 - 50 μg/24 h) 89.2 1 mg ODST cortisol (5 - 15 μg/dL) 15.7 8 mg ODST cortisol (5 - 15 μg/dL) 20.0 11 pm salivary cortisol × 2 (< 100 ng/dL) 156 and 151 Random cortisol (3 - 22 μg/dL) 17.3 Random ACTH (6 - 50 pg/mL) Undetectable CRH stimulation test No cortisol or ACTH response Articles © The authors | Journal compilation © J Endocrinol Metab and Elmer Press Inc™ | www.jofem.org 227 Mifepristone Use Prior to Cushing’s Surgery J Endocrinol Metab. 2015;5(3):226-228 Table 2. Adrenal Venous Sampling Site Cortisol (3 - 22 μg/dL) Epinephrine (< 84 pg/mL) Left adrenal gland 84.9 433 Right adrenal gland 56.5 1,911 Inferior vena cava 11.7 28 adrenal venous sampling. Aldosterone measurement in AVS, unique role. Also it would be interesting to explore potential reportedly used in case reports, could have provided impor- role of mifepristone preoperative preparation in patients with tant information during diagnosis, given the subtly low right pituitary Cushing’s syndrome. adrenal cortisol and low left adrenal epinephrine levels (likely from phrenic vein dilution) but based on size and hypercor- tisolism bilateral adrenal resection was indicated [2, 3]. Per- Disclosure sistent hypercortisolism increases the risk of perioperative morbidity by increasing infectious complications and de- The authors have nothing to disclose. layed tissue healing [4]. The options of outpatient manage- ment of hypercortisolism include ketoconazole, metyrapone and mifepristone. Ketoconazole could not be used due to drug References
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